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Background: The modern-day therapeutic landscape for follicular lymphoma (FL) includes a number of highly effective therapies. Patients and methods: We set out to determine progression-free survival (PFS) after front line, second line, and third line of therapy on the basis of relevant biological characteristics and therapeutic choices. Patients (n = 743, 51% females, median 60 years old) diagnosed with grade 1–2 FL between 1997 and 2016 in nine institutions were included. Results: The median PFS1, PFS2, and PFS3 were 8.1 years (95% confidence interval [CI]: 7–9.3 years), 4.2 years (95% CI: 2.8–5.6 years) and 2.2 years (95% CI 1.7–2.8 years). We found longer PFS1 for (1) females, (2) younger age, (3) lower-risk follicular lymphoma international prognostic index (FLIPI), (4) standard intensity (over low intensity) regimens and (5) immunochemotherapy strategies and (6) maintenance rituximab. We found a shorter PFS2 for patients who received front-line immunochemotherapy. Older age at diagnosis correlated with a shorter PFS3. Intensity of front-line chemotherapy, maintenance, or POD24 status did not correlate with PFS2 or PFS3 in this dataset. Interpretation: With current immunochemotherapy strategies, the natural course of FL is characterized by shorter-lasting remissions after each relapse. It will be interesting to see whether new therapies can alter this pattern.